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Here we aimed to delineate the complete causal pathway from a specific gut microorganism to bladder dysfunction and validate it as a therapeutic target. We combined analysis of human OAB\u2013IBS cohorts with a postinflammatory mouse model, integrating retrograde neuronal tracing, multiomics (16S rDNA and metabolomics), fecal microbiota transplantation, urodynamics, dorsal root ganglion (DRG) electrophysiology and pharmacological and\/or surgical interventions. We first confirmed a direct anatomical link, identifying dichotomized DRG neurons co-innervating the colon and bladder. Patients with OAB\u2013IBS and mice exhibited a shared gut dysbiosis characterized by\n                    <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    enrichment. This comorbidity occurred in the absence of local bladder inflammation or urinary colonization with\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    , confirming a functional, noninfectious mechanism. Fecal microbiota transplantation of\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    or patient microbiota causally exacerbated visceral hypersensitivity, the OAB phenotype and DRG hyperexcitability. Mechanistically,\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    enrichment shunted host tryptophan metabolism toward the serotonin (5-HT) pathway. The resulting excess 5-HT acted on specifically upregulated colonic 5-HT\n                    <jats:sub>3a<\/jats:sub>\n                    receptors to drive neuronal sensitization. Crucially, pharmacological blockade of the colonic 5-HT\n                    <jats:sub>3a<\/jats:sub>\n                    receptor or surgical severing of the mesenteric nerves reversed the bladder dysfunction and visceral hypersensitivity. Our findings delineate a novel pathway wherein\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    drives functional gut\u2013bladder comorbidity by promoting a gut-derived serotonergic signal that sensitizes shared afferent neurons, establishing the gut-specific 5-HT\n                    <jats:sub>3a<\/jats:sub>\n                    receptor as a key, druggable therapeutic target.\n                  <\/jats:p>","DOI":"10.1038\/s12276-026-01720-4","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T08:45:43Z","timestamp":1778229943000},"page":"1608-1625","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Akkermansia muciniphila drives viscero-visceral crosstalk via 5-HT3aR-mediated sensitization of dichotomizing gut\u2013bladder neurons"],"prefix":"10.1038","volume":"58","author":[{"given":"Qi","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rulin","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangrui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentai","family":"Shangguan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leqian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qishen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7751-4435","authenticated-orcid":false,"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2300-3583","authenticated-orcid":false,"given":"Bisheng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2026-4102","authenticated-orcid":false,"given":"Peng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"1720_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/S0090-4295(02)02243-4","volume":"61","author":"P Abrams","year":"2003","unstructured":"Abrams, P. et al. 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